Laboratoire de Glycochimie, des Antimicrobiens
et des Agroressources UMR 7378 CNRS

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Conférence : Hybridation of Mass Spectrometry and Infrared Ion Spectroscopy for Glycoanalytics

Dr. Isabelle Compagnon

Institut Lumière Matière. Université Lyon 1/CNRS. Villeurbanne. France.

Le 11 Jul 2019 à 14:00
A définir

Actualités et Publications

High resolution MALDI-TOF-MS and MS/MS: Application for the structural characterization of sulfated oligosaccharides,

Lesur, D.; Duhirwe, G.; Kovensky, J.

Eur. J. Mass Spectrom. 2019, 0.

Sulfated oligosaccharides are involved in important biological events that are often modulated by specific sequences and sulfation patterns, but their structural analysis remains challenging. Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) analysis of three different sulfated oligosaccharides (Fondaparinux, the octasulfated pentasaccharide, a disulfated heparin-derived tetrasaccharide 1, and an octasulfated maltoheptaose) 2 was performed using the 2-(4-hydroxyphenylazo)benzoic acid-tetramethylguanidinium (HABA-TMG2) matrix. High resolution mass spectrometry of the main ions observed was successful, and this was complemented by tandem mass spectrometry (MS/MS) analysis for structural assessment. Despite sulfate losses, fully sulfated molecular ions were observed and these allowed the determination of oligosaccharide structures: UA-GlcNAc-UA(2S)-AnhMan(6S) for compound 1 and (Glc6S)6-Glc (1S,6S) for compound 2.

A microscale double labelling of GAG oligosaccharides compatible with enzymatic treatment and mass spectrometry,

Przybylski, C.; Bonnet, V.; Vivès, R. R.

Chem. Commun. (Cambridge, U. K.) 2019, 55, 4182-4185.

A novel double labelling of glycosaminoglycans (GAG) oligosaccharides by thia-Michael addition and deuterium incorporation at the non-reducing and reducing ends, respectively, was introduced. This was demonstrated to be both compatible with the heparin microgram scale and amenable for mass spectrometry analysis, without impairing enzymatic activities such as heparinase I and sulfatase HSulf-2.

Lactose derivatives as potential inhibitors of pectin methylesterases,

L'Enfant, M.; Kutudila, P.; Rayon, C.; Domon, J.-M.; Shin, W.-H.; Kihara, D.; Wadouachi, A.; Pelloux, J.; Pourceau, G.; Pau-Roblot, C.

Int. J. Biol. Macromol. 2019, 132, 1140-1146.

The discovery of molecules that can inhibit the action of phytopathogens is essential to find alternative to current pesticides. Pectin methylesterases (PME), enzymes that fine-tune the degree of methylesterification of plant cell wall pectins, play a key role in the pathogenicity of fungi or bacteria. Here we report the synthesis of new lactoside derivatives and their analysis as potential PME inhibitors using three plants and one fungal PME. Because of its structure, abundance and reduced cost, lactose was chosen as a case study. Lactoside derivatives were obtained by TEMPO-mediated oxidation of methyl lactoside, followed by an esterification procedure. Three derivatives were synthesized: sodium (methyl-lactosid)uronate, methyl (methyl-lactosid)uronate and butyl (methyl-lactosid)uronate. The inhibition of the plant and pathogen enzyme activities by lactoside derivatives was measured in vitro, showing the importance of the substitution on lactose: methyl (methyl-lactosid)uronate was more efficient than butyl (methyl-lactosid)uronate. These results were confirmed by docking analysis showing the difference in the interaction between lactoside derivatives and PME proteins. In conclusion, this study identified novel inhibitors of pectin remodeling enzymes.

Synthesis of high molecular weight chitosan from chitin by mechanochemistry and aging,

Di Nardo, T.; Hadad, C.; Nguyen Van Nhien, A.; Moores, A.

Green Chem. 2019.

Chitosan can be obtained from the deacetylation of chitin. This process is however difficult and usually accompanied by depolymerization, affording low molecular weight chitosan. We report a novel path, relying on the combination of mechanochemistry and aging, to yield high molecular weight chitosan with minimal use of energy and solvent. This method is versatile and applicable to a number of chitin sources, including crude crustacean and insect shells, yielding deacetylation up to 98% and remarkably high molecular weights. Chitin deacetylation was studied by magic angle spinning nuclear magnetic resonance and molecular weight was estimated by viscometry. This process affords chitosan in a safer fashion and with less materials and energy usage compared to the classic hydrothermal one.

Unprecedented thiacalixarene fucoclusters strong inhibitors of Ebola cis-cell infection and HCMV-gB glycopro-tein/DC-SIGN C-type lectin interaction,

Taouai, M.; Porkolab, V.; Chakroun, K.; Cheneau, C.; Luczkowiak, J.; Abidi, R.; Lesur, D.; Cragg, P. J.; Halary, F.; Delgado, R.; Fieschi, F.; Benazza, M.

Bioconjug Chem 2019.

Glycan-protein interactions control numerous biological events from cell-cell recognition and signaling to pathogen host cell attachment for infections. To infect cells, some viruses bind to immune cells thanks to DC-SIGN (dendritic cell [DC]-specific ICAM3-grabbing non-integrin) C-type lectin expressed on dendrit-ic and macrophage cell membrane, via their envelope protein. Prevention of this infectious interaction is a serious therapeutic option. Here, we describe the synthesis of first water-soluble tetravalent fucocluster pseudopeptide-based thiacalixarene 1,3-alternate as viral antigen mimics designed for the inhibition of DC-SIGN, to prevent viral particle uptake. Their preparation exploits straightforward convergent strate-gies involving one pot Ugi four-component (Ugi-4CR) and azido-alkyne click chemistry reactions as key steps. Surface plasmon resonance showed strong inhibition of DC-SIGN interaction properties by tetrava-lent ligands designed with high relative potencies and beta avidity factors. All ligands block DC-SIGN active sites at nanomolar IC50 preventing cis-cell infection by Ebola viral particles pseudotyped with EBOV gly-coprotein (Zaire species of Ebola virus) on Jurkat cells that express DC-SIGN. In addition, we observed strong inhibition of DC-SIGN/human cytomegalovirus (HCMV)-gB recombinant glycoprotein interaction. This finding opens the way to the simple development of new models of water-soluble glycocluster-based thiacalixarene with wide range antimicrobial activities.

Solid-phase synthesis of molecularly imprinted polymer nanolabels: Affinity tools for cellular bioimaging of glycans,

Medina Rangel, P. X.; Laclef, S.; Xu, J.; Panagiotopoulou, M.; Kovensky, J.; Tse Sum Bui, B.; Haupt, K.

Scientific Reports 2019, 9, 3923.

Hyaluronic acid (HA) is a glycosaminoglycan that plays many roles in health and disease and is a key biomarker of certain cancers. Therefore, its detection at an early stage, by histochemical methods, is of importance. However, intracellular HA can be masked by other HA-binding macromolecules, rendering its visualization somehow problematic. We show that fluorescent molecularly imprinted polymer nanogels (MIP-NPs), can localize and detect intracellular HA. MIP-NPs were synthesized by solid-phase synthesis on glass beads (GBs). GBs were functionalized with terminal alkyne groups on which an azide derivative of the template molecule glucuronic acid was immobilized via click chemistry. Immobilization via the anomeric carbon left the template’s carboxyl moiety free to enable strong stoichiometric electrostatic interactions with a benzamidine-based functional monomer, to confer selective recognition to the MIP-NPs. Due to the two-point orientation of the template, the resulting MIP-NPs were endowed with improved binding site homogeneity and specificity, reminiscent of monoclonal antibodies. These synthetic antibodies were then applied for probing and staining HA, of which glucuronic acid is a substructure (epitope), on human epidermal cells. Their excellent sensitivity, small size and water compatibility, enabled the MIP-NPs to visualize HA, as evidenced by confocal fluorescence micrographs.

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